Reverse engineering and energetics of high frequency action potential generation
高频动作电位产生的逆向工程和能量学
基本信息
- 批准号:RGPIN-2018-06835
- 负责人:
- 金额:$ 2.04万
- 依托单位:
- 依托单位国家:加拿大
- 项目类别:Discovery Grants Program - Individual
- 财政年份:2020
- 资助国家:加拿大
- 起止时间:2020-01-01 至 2021-12-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
The proposal focuses on understanding cell excitability in challenging and extreme situations as a laboratory to understanding strategies devised by living systems to optimize energetics and maintain homeostasis, or a state of dynamical equilibrium. Cellular electrical signaling is based, with few exceptions, on a universal principle: controlled dissipation of ion gradients across a membrane that sustains low intracellular Na+ and extracellular K+ concentrations. These gradients provide the driving force for voltage spikes, or action potentials (APs). To maintain excitability, ion gradients must be restored by the chemical work of (ATP-fueled) Na+/K+ pumps, a process that preserves cellular homeostasis. This universal mode of operation is the basis of operation for axons in the central nervous system, and, in weakly electric fish such as Eigenmannia, it produces external electric currents by which the fish senses its environment. Operating under challenging conditions raises issues of energetics and strategies to maintain homeostasis.
Remarkably, throughout their lifetime, Eigenmannia continuously produce an oscillating dipole-like electric organ discharge (EOD) at a fixed individual specific frequency originating from columns of electrocyte cells. The species range is 200-500Hz. The organ's 1000 or so non-contractile cells are driven by releases of acetylcholine through the synaptic gap. The neural input ensures that APs fire synchronously, producing a highly regular EOD. Our first short term goal is to determine how this complex high frequency “device” produces an energy-efficient dipole oscillator. Our approach is to construct EODs from the cell up to the whole organ, remembering that understanding the cellular logistics of ion homeostasis is mandatory if the EOD is to be understood. In parallel, measurements of the EOD signal are being carried out in my collaborator's lab. The low intrinsic EOD variability has received little attention so far, but our examination promises fresh insights into EO design. The brain's input into the EO provides a high frequency signal via myelinated axons which must be robust. This connects to our second short term goal, investigating the response to sustained high frequency firing in axons not designed for that purpose, including those that have suffered mild damage. We want to understand how these myelinated neurons recover excitability and homeostasis.
The weakly electric fish is a fascinating model system for studying not only the energetics but the subcellular and broader level dynamics of high frequency excitability. The study of axons subjected to sustained abnormal firing or mildly damaged will reveal homeostatic design features. Our work guided by experiment and with continuous input from several biologists ensures that the predictions are well grounded and their impact extends beyond the realms of biophysics.
该提案侧重于了解细胞在具有挑战性和极端情况下的兴奋性,将其作为实验室来理解生命系统设计的策略,以优化能量学并维持动态平衡。除了少数例外,细胞电信号是基于一个普遍的原则:在维持低细胞内Na+和细胞外K+浓度的膜上控制离子梯度的消散。这些梯度提供了电压尖峰或动作电位(AP)的驱动力。为了保持兴奋性,离子梯度必须通过(三磷酸腺苷驱动的)Na+/K+泵的化学作用来恢复,这是一个维持细胞内稳态的过程。这种通用的操作模式是中枢神经系统轴突操作的基础,在像本征曼尼亚这样的弱电鱼类中,它会产生外部电流,鱼类通过它来感知环境。在具有挑战性的条件下运行会引发能量学问题和维持动态平衡的策略。
值得注意的是,在它们的一生中,本征曼尼亚不断地以固定的个体特定频率产生振荡的偶极样电器官放电(EOD),起源于电细胞柱。种的范围是200-500赫兹。该器官的大约1000个非收缩细胞是由通过突触间隙释放的乙酰胆碱驱动的。神经输入确保AP同步发射,产生高度规则的爆炸性爆炸。我们的第一个短期目标是确定这个复杂的高频“装置”如何产生一个节能的偶极振荡器。我们的方法是构建从细胞到整个器官的EOD,记住,如果要理解EOD,就必须了解离子稳态的细胞物流。与此同时,我的合作者的实验室正在进行排爆信号的测量。到目前为止,EOD的低内在变异性还没有得到多少关注,但我们的研究有望为EO设计提供新的见解。大脑对EO的输入通过有髓轴突提供高频信号,这些轴突必须是健壮的。这与我们的第二个短期目标有关,调查了非为此目的而设计的轴突对持续高频放电的反应,包括那些遭受轻微损伤的轴突。我们想了解这些有髓神经元是如何恢复兴奋性和内稳态的。
弱电鱼类是一个迷人的模型系统,不仅用于研究能量学,还用于研究高频兴奋性的亚细胞和更广泛的水平的动力学。对持续异常放电或轻微损伤的轴突的研究将揭示内稳态的设计特征。我们的工作以实验为指导,并得到了几位生物学家的持续投入,确保了预测是有良好基础的,其影响超出了生物物理学的领域。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Joos, Bela其他文献
Mechanosensitive Closed-Closed Transitions in Large Membrane Proteins: Osmoprotection and Tension Damping
- DOI:
10.1016/j.bpj.2009.08.054 - 发表时间:
2009-11-18 - 期刊:
- 影响因子:3.4
- 作者:
Boucher, Pierre-Alexandre;Morris, Catherine E.;Joos, Bela - 通讯作者:
Joos, Bela
Stimulation-induced ectopicity and propagation windows in model damaged axons.
- DOI:
10.1007/s10827-014-0521-9 - 发表时间:
2014-12 - 期刊:
- 影响因子:1.2
- 作者:
Lachance, Mathieu;Longtin, Andre;Morris, Catherine E.;Yu, Na;Joos, Bela - 通讯作者:
Joos, Bela
Calculating the Consequences of Left-Shifted Nav Channel Activity in Sick Excitable Cells
- DOI:
10.1007/164_2017_63 - 发表时间:
2018-01-01 - 期刊:
- 影响因子:0
- 作者:
Joos, Bela;Barlow, Benjamin M.;Morris, Catherine E. - 通讯作者:
Morris, Catherine E.
Coupled left-shift of Nav channels: modeling the Na+-loading and dysfunctional excitability of damaged axons
- DOI:
10.1007/s10827-012-0387-7 - 发表时间:
2012-10-01 - 期刊:
- 影响因子:1.2
- 作者:
Boucher, Pierre-Alexandre;Joos, Bela;Morris, Catherine E. - 通讯作者:
Morris, Catherine E.
Pore formation in a lipid bilayer under a tension ramp:: Modeling the distribution of rupture tensions
- DOI:
10.1529/biophysj.106.092023 - 发表时间:
2007-06-01 - 期刊:
- 影响因子:3.4
- 作者:
Boucher, Pierre-Alexandre;Joos, Bela;Fournier, Luc - 通讯作者:
Fournier, Luc
Joos, Bela的其他文献
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{{ truncateString('Joos, Bela', 18)}}的其他基金
Reverse engineering and energetics of high frequency action potential generation
高频动作电位产生的逆向工程和能量学
- 批准号:
RGPIN-2018-06835 - 财政年份:2022
- 资助金额:
$ 2.04万 - 项目类别:
Discovery Grants Program - Individual
Reverse engineering and energetics of high frequency action potential generation
高频动作电位产生的逆向工程和能量学
- 批准号:
RGPIN-2018-06835 - 财政年份:2021
- 资助金额:
$ 2.04万 - 项目类别:
Discovery Grants Program - Individual
Reverse engineering and energetics of high frequency action potential generation
高频动作电位产生的逆向工程和能量学
- 批准号:
RGPIN-2018-06835 - 财政年份:2019
- 资助金额:
$ 2.04万 - 项目类别:
Discovery Grants Program - Individual
Reverse engineering and energetics of high frequency action potential generation
高频动作电位产生的逆向工程和能量学
- 批准号:
RGPIN-2018-06835 - 财政年份:2018
- 资助金额:
$ 2.04万 - 项目类别:
Discovery Grants Program - Individual
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Reverse engineering and energetics of high frequency action potential generation
高频动作电位产生的逆向工程和能量学
- 批准号:
RGPIN-2018-06835 - 财政年份:2022
- 资助金额:
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Discovery Grants Program - Individual
Reverse engineering and energetics of high frequency action potential generation
高频动作电位产生的逆向工程和能量学
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